NCT00295919已完成1 期
Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb™ (LXS) Oral Powder in Patients With Recurrent or Resistant Neuroblastoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 18
- 主要终点
- Toxicity of HPR/LXS oral powder
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as fenretinide LXS, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of fenretinide LXS in treating patients with recurrent, refractory, or persistent neuroblastoma.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of fenretinide (4-HPR) Lym-X-Sorb™ (LXS) oral powder (4-HPR/LXS oral powder) in patients with recurrent, refractory, or persistent neuroblastoma.
- Define the toxicities of 4-HPR/LXS oral powder in these patients.
- Determine the plasma pharmacokinetics of 4-HPR/LXS oral powder and its metabolites in these patients.
- Determine the tolerability of the combination of ketoconazole and 4-HPR/LXS oral powder in these patients.
Secondary
- Determine the response rate in patients treated with 4-HPR/LXS oral powder.
- Determine the level of 4-HPR/LXS oral powder in normal peripheral blood mononuclear cells (PBMC) as a tumor cell surrogate tissue.
- Determine plasma levels of 4-HPR/LXS oral powder when given in combination with ketoconazole.
- Determine whether ketoconazole increases 4-HPR/LXS oral powder plasma levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of neuroblastoma either by histology and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
- •High-risk disease, as evidenced by ≥ 1 of the following:
- •Recurrent/progressive disease at any time
- •Refractory disease (i.e., less than a partial response to frontline therapy)
- •No biopsy required
- •Persistent disease after at least a partial response to frontline therapy (i.e., patient has had at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT scan/MRI, or bone marrow)
- •Biopsy of at least one residual site demonstrating viable neuroblastoma required
- •Patients must have ≥ 1 of the following sites of disease:
- •Measurable tumor, defined as ≥ 2 cm in at least 1 dimension by MRI, CT scan, or x-ray OR ≥ 1 cm in at least 1 dimension by spiral CT scan
- •For persistent disease, a biopsy of bone and/or soft tissue site seen on CT/MRI must have been done to demonstrate viable neuroblastoma
- •If lesion was irradiated, biopsy must be done ≥ 2 weeks after radiation completed
- •MIBG scan with positive uptake at ≥ 1 site
- •For persistent disease, a biopsy of an MIBG-positive site must have been done to demonstrate viable neuroblastoma
- •If lesion was irradiated, biopsy must be done at least 2 weeks after radiation completed
- •Tumor cells on routine morphology (not by neuron-specific enolase staining only) of bilateral bone marrow aspirate and/or biopsy on one bone marrow sample
- •Patients enrolled in group I may have had a prior relapse or progression, even if they have no measurable or evaluable tumor sites at time of study entry, including any of the following:
- •No tumor sites on all evaluations
- •Non-measurable tumor on MRI /CT scan and/or measurable tumor on CT/MRI that was previously irradiated
- •MIBG-avid site that was previously irradiated
- •No CNS parenchymal or meningeal-based lesions
- •Skull-based tumor lesions with or without intracranial soft tissue extension allowed provided there are no neurological signs or symptoms or hydrocephalus related to the lesion
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-2
- •Life expectancy ≥ 2 months
- •Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
- •ANC ≥ 500/mm^3
- •Platelet count ≥ 50,000/mm^3 (transfusion independent [ i.e., ≥ 1 week since last platelet transfusion])
- •Creatinine ≤ 1.5 times normal for age as follows:
- •No greater than 0.8 mg/dL (for patients 5 years of age and under)
- •No greater than 1.0 mg/dL (for patients 6-10 years of age)
- •No greater than 1.2 mg/dL (for patients 11-15 years of age)
- •No greater than 1.5 mg/dL (for patients over 15 years of age)
- •Ejection fraction ≥ 55% by echocardiogram or MUGA OR fractional shortening ≥ 27% by echocardiogram
- •Bilirubin ≤ 1.5 times normal
- •ALT and AST ≤ 3 times normal (for ALT, upper limit of normal is 45 U/L)
- •Triglycerides < 300 mg/dL (fasting or random plasma test)
- •Calcium < 11.6 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use 2 methods of effective contraception during and for 2 months after completion of study treatment
- •Normal lung function (i.e., no dyspnea at rest or oxygen requirement)
- •Seizure disorder allowed provided seizures are controlled on anticonvulsants that are not contraindicated
- •No EKG abnormality severe enough to justify cardiac medications
- •No skin toxicity > grade 1
- •No hematuria and/or proteinuria > +1 on urinalysis
- •No known allergy to soy products
- •No known severe allergy or sensitivity to wheat gluten
- •No known history of intolerance to ketoconazole (group II)
- •PRIOR CONCURRENT THERAPY:
- 另有 27 项未显示
排除标准
- 未提供
研究组 & 干预措施
Single Group
Experimental
干预措施: ketoconazole (Drug)
Single Group
Experimental
干预措施: pharmacological study (Other)
Single Group
Experimental
干预措施: laboratory biomarker analysis (Other)
Single Group
Experimental
干预措施: fenretinide lipid matrix (Drug)
结局指标
主要结局
Toxicity of HPR/LXS oral powder
时间窗: Day 1 of therapy to 16 days after last day of therapy
Plasma pharmacokinetics of 4-HPR/LXS oral powder and its metabolites
时间窗: Day 0 of protocol therapy through Day 6 of Course 6
Maximum tolerated dose
时间窗: Day 1 of therapy to 16 days after last day of therapy
Tolerability of the combination of ketoconazole and 4-HPR/LXS oral powder
时间窗: Day 1 of therapy to 16 days after last day of therapy
次要结局
未报告次要终点
研究者
Nant Operations Center
NANT Consortium
Children's Hospital Los Angeles
研究点 (18)
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